THE OCUL AR FINDI NGS IN INFAN TILE SPASM S CREIG
S.
HoYT
III, MD
SAN FRANCIS CO, CALIFOR NIA
IN 1841, West 1 publishe d the first account of a patient with infantil e spasms and accomp anying mental subnorm ality. His graphic description of this form of infantil e myoclonic seizures is made even more poignan t when one realized he was describi ng his son. In infantil e spasms one usually sees lightnin g fast nodding of the head, often with extensio n or flexion of the trunk and frequen tly also of the arms. The onset of these spasms has been observe d in the neonata l period, but more characte risticall y they become apparen t between 3 and 9 months of age. 2 A child who has infantil e spasms is likely to have them many times a day, even exceeding a thousan d times daily.
the more common docume nted causative factors are tuberou s sclerosis, phenylk etonuria and other inborn errors of metabol ism, immuni zation encepha lopathy , and apparently any devasta ting disease of the central nervous system in young children. 2 The need for detailed etiologic investig ations in order to help establis h a diagnos is, and ultimately the prognos is, is, therefore, well recognized. 5 ·6 This report describe s the ophthal moscopic findings in 44 consecu tive patients presenti ng with infantil e spasms. In ten cases the etiology could be ascertai ned as the result of this ophthal mic examina tion. MATER IALS AND METHO DS
These attacks do not appear to be the manifes tation of any single This study was based on the findmetabol ic or structur al alteratio n ings of 44 consecu tive patients with of the nervous system, but rather infantile spasms who were admitted they are a nonspecific expressi on of to the Univers ity of Californ ia damage to an immatu re brain. 3 Medical Center, San Francisc o, for Thus, infantil e spasms become diagnos tic studies. There were 30 milder and less frequen t with age. boys and 14 girls; ages at the time However, the high incidenc e of of examina tion ranged from 6 weeks serious mental retardat ion is a to 28 months. major concern in establis hing the prognos is of these children . 4 The ophthal mic examina tion included an attempt to see if the In most cases, these infants suffer patient would fix and follow a light, from some form of brain damage or an evaluati on of motor alignme nt, specific disease process. 2 •4 Among externa l examina tion of the eyes with a hand-he ld magnify ing lens, and the respons e of the pupils to Submitted for publication Jan 31, 1979. light. Examin ation of the ocular fundi was carried out after pupilFrom the Departmen t of Pediatric Ophthalmo logy, University of California Medical Center. lary dilatatio n with phenyle phrine hydrochloride (Neoesynephrine) 2WYo Reprint requests to Director of Pediatric Ophthalmology, Room U-490, University of California and tropicam ide (Mydriacyl) 1%. Medical Center, San Francisco, CA 94143 (Dr Ophthal moscop y was completed Hoyt). 1794
VOLUME OCTOBER
86 1979
INFANTILE SPASMS
1795
Fig 1.-The typical flat retinal hamartoma is seen contiguous with the disc.
using a Schultz-Crock indirect ophthalmoscopy and a Nikon 20-D aspheric lens. RESULTS
In 34 cases the ophthalmic examination did not reveal any ocular findings that assisted in the determination of the etiology of the patient's infantile spasms. In the other ten cases the ocular findings were a major factor in establishing a diagnosis. In eight cases, one or more retinal hamartomas were identified. A diagnosis of tuberous sclerosis was
suggested by these findings and subsequently established in all eight patients by genetic history, dermatologic examination, and/or the demonstration of subependymal calcifications by computerized tomography (CT scanning) of the brain. The retinal lesions were primarily flat, small, and semitransparent (Fig 1), although in one case the more dramatic elevated, nodularshaped lesion, or so-called mulberry tumor, was seen (Fig 2). In two cases the ocular findings consisted of multiple, various sized, punched-out lesions of the choroid and retina (Fig 3), colobomas of the optic nerves, and persistent pupil-
CREIG S. HOYT III
1796
OPHTH AAO
Fig 2.-The more elevated and nodular retinal lesion seen in older children with tuberous sclerosis is shown.
lary remnants. These findings in a female patient with infantile spasms are pathognomonic of Aicardi's syndrome. 7 The other cardinal feature of this often lethal syndrome is agenesis of the corpus callosum. 8 Computerized tomography of the brain documented this in both of these patients. DISCUSSION
West's syndrome, or the clinical triad of infantile spasms, hypsarrhythmia (a characteristic electroencephalographic pattern), and mental retardation, is a symptom
complex and not a specific disease entity. The known etiologic diagnoses are diverse. It has generally been accepted that in approximately one half of the cases of infantile spasms no cause can be established.2·9 However, in a recent study of 37 patients with infantile spasms, computerized tomography of the brain was abnormal in 30. 5 In their discussion of this study the authors stated, "the family history and the clinical and complementary examinations in general use are often inadequate in assessing the primary nature of this syndrome."
VOLUME OCTOBER
86 1979
INFANTILE SPASMS
1797
Fig 3.-The typical retinal lesions seen in Aicardi's syndrome are the multiple punched·out chorioretinal lesions primarily confined to the posterior pole.
They urged that cerebral computer- establishing the diagnosis of tubized tomography be utilized rou- erous sclerosis in infancy. There tinely in the evaluation of these are five essential signs of tuberous patients. The usefulness of CT sclerosis: epilepsy, mental retardascanning cannot be denied. How- tion, adenoma sebaceum, intracereever, my study suggests that in at bral calcifi«;ations, and hamartomas least 20% of cases of infantile spasms of the retina.H Two of these, epia careful ophthalmologic examina- lepsy and mental retardation, are tion will establish an etiologic diag- not specific enough to establish a diagnosis. Two others, adenoma nosis. sebaceum and intracerebral calcifiThe high incidence of tuberous cations, occur infrequently in insclerosis among infants with infan- fancy and are, therefore, not likely tile spasms has been emphasized to be seen in the patients presentby several authors. 5 •10 It may be ing for evaluation of infantile even higher than generally recog- spasms. Thus, the identification of nized because of the difficulty in a retinal hamartoma may be the
1798
CREIG S. HOYT III
only clinical feature of sufficient specificity to establish a diagnosis of tuberous sclerosis in the first few years of life. The characteristic ophthalmologic lesion of tuberous sclerosis is the "phakoma," a name given by Van der Hoeve 12 to retinal tumors situated at the level of the posterior pole. Opinions differ with respect to the frequency of these retinal lesions.11· 13 •14 It has been assessed at less than 3-4%11 to greater than 50%.13.14 The failure of some authors to recognize that the mulberry form of lesion is not the only morphologic appearance of a retinal hamartoma probably accounts for this discrepancy. Two basic varieties of retinal tumors or hamartomas in tuberous sclerosis have been described in the literature.12 - 15 One is relatively flat, soft or smooth-appearing, and semitranslucent with poorly defined boundaries. The other is the more familiar, elevated multinodular lesion that has been compared in appearance to tapioca, mulberries, or salmon eggs. 14 When located near the disc, these lesions mimic hyaline bodies or giant drusen. In a recent study of 56 patients with tuberous sclerosis and retinal lesions, the flat, semitransparent hamartoma was seen in 31. These authors emphasized that the color of these lesions was often not meaningfully different from the background of the fundus. Furthermore, they stressed that these lesions could be easily overlooked if the examination was only carried out using a direct ophthalmoscope. In this same paper the evolution of a flat, noncalcified-appearing, semitransparent retinal lesion into
OPHTH AAO
an elevated, nodular, and apparently calcified lesion was documented during a period of observation of more than two decades. This would seem to lend weight to the thesis originally proposed by Falls16 that the typical grapelike or mulberrycluster-like lesion was actually a late stage of the originally flat lseion. My experience in examining infants with West's syndrome and tuberous sclerosis is in agreement with these observations. In seven of the eight patients I examined with tuberous sclerosis the retinal lesions were most often flat, small, and difficult to see. Moreover, they were not confined to the posterior pole but were seen even near the equator. Only in one patient was the classic mulberry lesion seen, and this was in a child 26 months old. I suspect, therefore, that Falls was correct; most, if not all, mulberry-like lesions evolve from a faint, flat, semitransparent one. In any case, the retinal lesion of tuberous sclerosis in infancy is a flat lesion that requires careful examination with an indirect ophthalmoscope in order to be seen. Children with infantile spasms may have myoclonic seizures so frequently that ophthalmoscopic examination is difficult, if not, impossible. In these cases I performed the examination when the patient was sedated (usually at the same time as a CT scan was performed). In 1965, a syndrome of infantile spasms, agenesis of the corpus callosum, and chorioretinopathy was described by Aicardi et al.8 Subsequently, more than 70 cases of this entity have been described and referred to as Aicardi's syndrome. The chorioretinal lesions are a con-
VOLUME OCTOBER
86 1979
1799
INFANTILE SPASMS
stant finding and are considered by Aicardi to be pathognomonic of the condition. The essential role of the ophthalmologist in establishing this diagnosis has been emphasized in the European ophthalmic literature for sometime, 17 but it has only recently been detailed in the English language ophthalmic literature.7 The chorioretinal lesions may vary in size from less than onetenth of a disc diameter to twice the normal size of an optic disc. The lesions may be well-defined circular white lacunae with minimal pigmentation at their borders, or less commonly, they appear as illdefined lesions with irregular pigment clumping. In general, all of the lesions cluster around the disc and decrease in size and number as one approaches the periphery of the fund us. 7'1 7 The exact nature of these lesions is uncertain, but they do not appear to be the consequence of intrauterine infection. 8 The pathologic examination of an eye from an infant with Aicardi's syndrome reported gaps in the retinal pigment epithelium, areas of intact but depigmented epithelium, and gross choroidal atrophy. 18 The retina was essentially undisturbed. Other ocular findings in this syndrome are microphthalmia, persistent pupillary membrane, and colobomas of the optic nerve and choroid. The cause of this syndrome is unknown. Any sucessful proposal concerning the pathogenesis must take into account its occurrence only in females, the lack of familial incidence, and the widespread involvement of the brain, eye, and skeletal system. It has been suggested that the causative factor
responsible for Aicardi's syndrome must exert its effect during the fourth or fifth week of intrauterine life.l 8 •
SUMMARY The results of this study suggest that a careful ophthalmoscopic examination of children with infantile spasms will help to establish an etiologic diagnosis in at least 20% of cases. The two clinical entities identifiable by this examination are tuberous sclerosis and Aicardi's syndrome. It is emphasized that the retinal hamartomas of tuberous sclerosis seen in infancy are flat, semitransparent, and small. The mulberrylike lesion is distinctly unusual in this age group. The essential ocular feature of Aicardi's syndrome is a chorioretinopathy of the posterior pole. This may be accompanied by microphthalmus, persistent pupillary remnant, and colobomas of the optic nerve and choroid. Diagnosis of either of these two entities is helpful in establishing the prognosis for a child with infantile spasms since both of these disorders usually lead to severe neurologic handicap and premature death. Moreover, genetic counseling is essential for the family suffering with this tragic disorder. Tuberous sclerosis is inherited as an irregular dominant trait. The genetic interpretation of sporadic cases, which are in the majority, is difficult due to the presence of unrecognized incomplete or "fruste" forms within families. On the other hand, Aicardi's syndrome has never been reported to be familial and future pregnancies can be undertaken without fear of producing another child with infantile spasms.
CREIG S. HOYT III
1800
REFERENCES 1. West WJ: Letter to the editor. Lancet 1:724, 1841.
2. Jeavons PM, Bower BD: Infantile spasms: A review of the literature and a study of 112 cases. Clin Dev Med 15:1-80, 1964. 3. Pollack MA, Golden GS, Schmidt R, Davis JA, Leeds N: Infantile spasms in Down's syndrome: A report of 5 cases and review of the literature. Ann Neurol 3:406408, 1978. 4. Jeavons PM, Harper JR, Bower BD: Longterm prognosis in infantile spasms: A follow-up report on 112 cases. Dev Med Child · Neurol 12:413-421, 1970. 5. Gastaut H, Gastaut JL, Regis H, Bernard R, Pinsard N, Saint-Jean M, Roger J, Dravet C: Computerized tomography in the study of West's syndrome. Dev Med Child · Neurol 20:21-27, 1978. 6. Charlton MH, Melinger JF: Infantile spasms and hypsarrhythmia. Electroencephalogr Clin Neurophysiol 29:413-418, 1970. 7. Hoyt CS, Billson F, Ouvrier R, Wise G: Ocular features of Aicardi's syndrome. Arch Ophthalmol 96:291-295, 1978. 8. Aicardi J, Lefebvre J, Lerique-Loechlin A: A new syndrome: Spasms in flexion, callosal agenesis, ocular abnormalities. Electroencephalogr Clin Neurophysiol 29:413418, 1970. 9. Millichap JG, Bicuford RG, Klass DW, Backus RE: Infantile spasms, hypsarrhyth-
OPHTH AAO
mia, mental retardation: A study of etiologic factors in 61 patients. Epilepsia 3:188-197, 1962. 10. Synder CH: Infantile spasms: Favorable response to steroid therapy. JAMA 201: 198-200, 1967. 11. Critchley M, Earl CJC: Tuberous sclerosis and allied conditions. Brain 55:311-346, 1932. 12. Van Der Hoeve J: Augengeschwultse bei der tuberosen hirnsklerose (Bourneville). Albrecht von Graefes Arch Klin Ophthalmol 105:880-898, 1921. 13. Lagos JC, Gomez MR: Tuberous sclerosis: Reappraisal of a clinical entity. Proc Staff Meet Mayo Clin 42:26-49, 1967. 14. Nyboer JH, Robertson DM, Gomez MR: Retinal lesions in tuberous sclerosis. Arch Ophthalmol 94:1277-1280, 1976. 15. Kirby TJ: Ocular phakomatoses. Am J Med Sci 222:227-239, 1951. 16. Falls HF (in discussion), McClean JM: Glial tumors of the retina in relation to tuberous sclerosis. Trans Am Ophthalmol Soc 53:209-217, 1955. 17. Hammami H, Streiff EB, DeWolff E: Contribution a la connaissance du syndrome D' Aicardi et coli. Bull Mem Soc Fr Ophtalmol 85:598-614, 1972. 18. DeJong JGY, Delleman JW, Houben M: Agenesis of the corpus callosum, infantile spasms, ocular anomalies (Aicardi's syndrome). Neurology 26:1152-1158, 1976.
S.
HoYT
III, MD
SAN FRANCIS CO, CALIFOR NIA
IN 1841, West 1 publishe d the first account of a patient with infantil e spasms and accomp anying mental subnorm ality. His graphic description of this form of infantil e myoclonic seizures is made even more poignan t when one realized he was describi ng his son. In infantil e spasms one usually sees lightnin g fast nodding of the head, often with extensio n or flexion of the trunk and frequen tly also of the arms. The onset of these spasms has been observe d in the neonata l period, but more characte risticall y they become apparen t between 3 and 9 months of age. 2 A child who has infantil e spasms is likely to have them many times a day, even exceeding a thousan d times daily.
the more common docume nted causative factors are tuberou s sclerosis, phenylk etonuria and other inborn errors of metabol ism, immuni zation encepha lopathy , and apparently any devasta ting disease of the central nervous system in young children. 2 The need for detailed etiologic investig ations in order to help establis h a diagnos is, and ultimately the prognos is, is, therefore, well recognized. 5 ·6 This report describe s the ophthal moscopic findings in 44 consecu tive patients presenti ng with infantil e spasms. In ten cases the etiology could be ascertai ned as the result of this ophthal mic examina tion. MATER IALS AND METHO DS
These attacks do not appear to be the manifes tation of any single This study was based on the findmetabol ic or structur al alteratio n ings of 44 consecu tive patients with of the nervous system, but rather infantile spasms who were admitted they are a nonspecific expressi on of to the Univers ity of Californ ia damage to an immatu re brain. 3 Medical Center, San Francisc o, for Thus, infantil e spasms become diagnos tic studies. There were 30 milder and less frequen t with age. boys and 14 girls; ages at the time However, the high incidenc e of of examina tion ranged from 6 weeks serious mental retardat ion is a to 28 months. major concern in establis hing the prognos is of these children . 4 The ophthal mic examina tion included an attempt to see if the In most cases, these infants suffer patient would fix and follow a light, from some form of brain damage or an evaluati on of motor alignme nt, specific disease process. 2 •4 Among externa l examina tion of the eyes with a hand-he ld magnify ing lens, and the respons e of the pupils to Submitted for publication Jan 31, 1979. light. Examin ation of the ocular fundi was carried out after pupilFrom the Departmen t of Pediatric Ophthalmo logy, University of California Medical Center. lary dilatatio n with phenyle phrine hydrochloride (Neoesynephrine) 2WYo Reprint requests to Director of Pediatric Ophthalmology, Room U-490, University of California and tropicam ide (Mydriacyl) 1%. Medical Center, San Francisco, CA 94143 (Dr Ophthal moscop y was completed Hoyt). 1794
VOLUME OCTOBER
86 1979
INFANTILE SPASMS
1795
Fig 1.-The typical flat retinal hamartoma is seen contiguous with the disc.
using a Schultz-Crock indirect ophthalmoscopy and a Nikon 20-D aspheric lens. RESULTS
In 34 cases the ophthalmic examination did not reveal any ocular findings that assisted in the determination of the etiology of the patient's infantile spasms. In the other ten cases the ocular findings were a major factor in establishing a diagnosis. In eight cases, one or more retinal hamartomas were identified. A diagnosis of tuberous sclerosis was
suggested by these findings and subsequently established in all eight patients by genetic history, dermatologic examination, and/or the demonstration of subependymal calcifications by computerized tomography (CT scanning) of the brain. The retinal lesions were primarily flat, small, and semitransparent (Fig 1), although in one case the more dramatic elevated, nodularshaped lesion, or so-called mulberry tumor, was seen (Fig 2). In two cases the ocular findings consisted of multiple, various sized, punched-out lesions of the choroid and retina (Fig 3), colobomas of the optic nerves, and persistent pupil-
CREIG S. HOYT III
1796
OPHTH AAO
Fig 2.-The more elevated and nodular retinal lesion seen in older children with tuberous sclerosis is shown.
lary remnants. These findings in a female patient with infantile spasms are pathognomonic of Aicardi's syndrome. 7 The other cardinal feature of this often lethal syndrome is agenesis of the corpus callosum. 8 Computerized tomography of the brain documented this in both of these patients. DISCUSSION
West's syndrome, or the clinical triad of infantile spasms, hypsarrhythmia (a characteristic electroencephalographic pattern), and mental retardation, is a symptom
complex and not a specific disease entity. The known etiologic diagnoses are diverse. It has generally been accepted that in approximately one half of the cases of infantile spasms no cause can be established.2·9 However, in a recent study of 37 patients with infantile spasms, computerized tomography of the brain was abnormal in 30. 5 In their discussion of this study the authors stated, "the family history and the clinical and complementary examinations in general use are often inadequate in assessing the primary nature of this syndrome."
VOLUME OCTOBER
86 1979
INFANTILE SPASMS
1797
Fig 3.-The typical retinal lesions seen in Aicardi's syndrome are the multiple punched·out chorioretinal lesions primarily confined to the posterior pole.
They urged that cerebral computer- establishing the diagnosis of tubized tomography be utilized rou- erous sclerosis in infancy. There tinely in the evaluation of these are five essential signs of tuberous patients. The usefulness of CT sclerosis: epilepsy, mental retardascanning cannot be denied. How- tion, adenoma sebaceum, intracereever, my study suggests that in at bral calcifi«;ations, and hamartomas least 20% of cases of infantile spasms of the retina.H Two of these, epia careful ophthalmologic examina- lepsy and mental retardation, are tion will establish an etiologic diag- not specific enough to establish a diagnosis. Two others, adenoma nosis. sebaceum and intracerebral calcifiThe high incidence of tuberous cations, occur infrequently in insclerosis among infants with infan- fancy and are, therefore, not likely tile spasms has been emphasized to be seen in the patients presentby several authors. 5 •10 It may be ing for evaluation of infantile even higher than generally recog- spasms. Thus, the identification of nized because of the difficulty in a retinal hamartoma may be the
1798
CREIG S. HOYT III
only clinical feature of sufficient specificity to establish a diagnosis of tuberous sclerosis in the first few years of life. The characteristic ophthalmologic lesion of tuberous sclerosis is the "phakoma," a name given by Van der Hoeve 12 to retinal tumors situated at the level of the posterior pole. Opinions differ with respect to the frequency of these retinal lesions.11· 13 •14 It has been assessed at less than 3-4%11 to greater than 50%.13.14 The failure of some authors to recognize that the mulberry form of lesion is not the only morphologic appearance of a retinal hamartoma probably accounts for this discrepancy. Two basic varieties of retinal tumors or hamartomas in tuberous sclerosis have been described in the literature.12 - 15 One is relatively flat, soft or smooth-appearing, and semitranslucent with poorly defined boundaries. The other is the more familiar, elevated multinodular lesion that has been compared in appearance to tapioca, mulberries, or salmon eggs. 14 When located near the disc, these lesions mimic hyaline bodies or giant drusen. In a recent study of 56 patients with tuberous sclerosis and retinal lesions, the flat, semitransparent hamartoma was seen in 31. These authors emphasized that the color of these lesions was often not meaningfully different from the background of the fundus. Furthermore, they stressed that these lesions could be easily overlooked if the examination was only carried out using a direct ophthalmoscope. In this same paper the evolution of a flat, noncalcified-appearing, semitransparent retinal lesion into
OPHTH AAO
an elevated, nodular, and apparently calcified lesion was documented during a period of observation of more than two decades. This would seem to lend weight to the thesis originally proposed by Falls16 that the typical grapelike or mulberrycluster-like lesion was actually a late stage of the originally flat lseion. My experience in examining infants with West's syndrome and tuberous sclerosis is in agreement with these observations. In seven of the eight patients I examined with tuberous sclerosis the retinal lesions were most often flat, small, and difficult to see. Moreover, they were not confined to the posterior pole but were seen even near the equator. Only in one patient was the classic mulberry lesion seen, and this was in a child 26 months old. I suspect, therefore, that Falls was correct; most, if not all, mulberry-like lesions evolve from a faint, flat, semitransparent one. In any case, the retinal lesion of tuberous sclerosis in infancy is a flat lesion that requires careful examination with an indirect ophthalmoscope in order to be seen. Children with infantile spasms may have myoclonic seizures so frequently that ophthalmoscopic examination is difficult, if not, impossible. In these cases I performed the examination when the patient was sedated (usually at the same time as a CT scan was performed). In 1965, a syndrome of infantile spasms, agenesis of the corpus callosum, and chorioretinopathy was described by Aicardi et al.8 Subsequently, more than 70 cases of this entity have been described and referred to as Aicardi's syndrome. The chorioretinal lesions are a con-
VOLUME OCTOBER
86 1979
1799
INFANTILE SPASMS
stant finding and are considered by Aicardi to be pathognomonic of the condition. The essential role of the ophthalmologist in establishing this diagnosis has been emphasized in the European ophthalmic literature for sometime, 17 but it has only recently been detailed in the English language ophthalmic literature.7 The chorioretinal lesions may vary in size from less than onetenth of a disc diameter to twice the normal size of an optic disc. The lesions may be well-defined circular white lacunae with minimal pigmentation at their borders, or less commonly, they appear as illdefined lesions with irregular pigment clumping. In general, all of the lesions cluster around the disc and decrease in size and number as one approaches the periphery of the fund us. 7'1 7 The exact nature of these lesions is uncertain, but they do not appear to be the consequence of intrauterine infection. 8 The pathologic examination of an eye from an infant with Aicardi's syndrome reported gaps in the retinal pigment epithelium, areas of intact but depigmented epithelium, and gross choroidal atrophy. 18 The retina was essentially undisturbed. Other ocular findings in this syndrome are microphthalmia, persistent pupillary membrane, and colobomas of the optic nerve and choroid. The cause of this syndrome is unknown. Any sucessful proposal concerning the pathogenesis must take into account its occurrence only in females, the lack of familial incidence, and the widespread involvement of the brain, eye, and skeletal system. It has been suggested that the causative factor
responsible for Aicardi's syndrome must exert its effect during the fourth or fifth week of intrauterine life.l 8 •
SUMMARY The results of this study suggest that a careful ophthalmoscopic examination of children with infantile spasms will help to establish an etiologic diagnosis in at least 20% of cases. The two clinical entities identifiable by this examination are tuberous sclerosis and Aicardi's syndrome. It is emphasized that the retinal hamartomas of tuberous sclerosis seen in infancy are flat, semitransparent, and small. The mulberrylike lesion is distinctly unusual in this age group. The essential ocular feature of Aicardi's syndrome is a chorioretinopathy of the posterior pole. This may be accompanied by microphthalmus, persistent pupillary remnant, and colobomas of the optic nerve and choroid. Diagnosis of either of these two entities is helpful in establishing the prognosis for a child with infantile spasms since both of these disorders usually lead to severe neurologic handicap and premature death. Moreover, genetic counseling is essential for the family suffering with this tragic disorder. Tuberous sclerosis is inherited as an irregular dominant trait. The genetic interpretation of sporadic cases, which are in the majority, is difficult due to the presence of unrecognized incomplete or "fruste" forms within families. On the other hand, Aicardi's syndrome has never been reported to be familial and future pregnancies can be undertaken without fear of producing another child with infantile spasms.
CREIG S. HOYT III
1800
REFERENCES 1. West WJ: Letter to the editor. Lancet 1:724, 1841.
2. Jeavons PM, Bower BD: Infantile spasms: A review of the literature and a study of 112 cases. Clin Dev Med 15:1-80, 1964. 3. Pollack MA, Golden GS, Schmidt R, Davis JA, Leeds N: Infantile spasms in Down's syndrome: A report of 5 cases and review of the literature. Ann Neurol 3:406408, 1978. 4. Jeavons PM, Harper JR, Bower BD: Longterm prognosis in infantile spasms: A follow-up report on 112 cases. Dev Med Child · Neurol 12:413-421, 1970. 5. Gastaut H, Gastaut JL, Regis H, Bernard R, Pinsard N, Saint-Jean M, Roger J, Dravet C: Computerized tomography in the study of West's syndrome. Dev Med Child · Neurol 20:21-27, 1978. 6. Charlton MH, Melinger JF: Infantile spasms and hypsarrhythmia. Electroencephalogr Clin Neurophysiol 29:413-418, 1970. 7. Hoyt CS, Billson F, Ouvrier R, Wise G: Ocular features of Aicardi's syndrome. Arch Ophthalmol 96:291-295, 1978. 8. Aicardi J, Lefebvre J, Lerique-Loechlin A: A new syndrome: Spasms in flexion, callosal agenesis, ocular abnormalities. Electroencephalogr Clin Neurophysiol 29:413418, 1970. 9. Millichap JG, Bicuford RG, Klass DW, Backus RE: Infantile spasms, hypsarrhyth-
OPHTH AAO
mia, mental retardation: A study of etiologic factors in 61 patients. Epilepsia 3:188-197, 1962. 10. Synder CH: Infantile spasms: Favorable response to steroid therapy. JAMA 201: 198-200, 1967. 11. Critchley M, Earl CJC: Tuberous sclerosis and allied conditions. Brain 55:311-346, 1932. 12. Van Der Hoeve J: Augengeschwultse bei der tuberosen hirnsklerose (Bourneville). Albrecht von Graefes Arch Klin Ophthalmol 105:880-898, 1921. 13. Lagos JC, Gomez MR: Tuberous sclerosis: Reappraisal of a clinical entity. Proc Staff Meet Mayo Clin 42:26-49, 1967. 14. Nyboer JH, Robertson DM, Gomez MR: Retinal lesions in tuberous sclerosis. Arch Ophthalmol 94:1277-1280, 1976. 15. Kirby TJ: Ocular phakomatoses. Am J Med Sci 222:227-239, 1951. 16. Falls HF (in discussion), McClean JM: Glial tumors of the retina in relation to tuberous sclerosis. Trans Am Ophthalmol Soc 53:209-217, 1955. 17. Hammami H, Streiff EB, DeWolff E: Contribution a la connaissance du syndrome D' Aicardi et coli. Bull Mem Soc Fr Ophtalmol 85:598-614, 1972. 18. DeJong JGY, Delleman JW, Houben M: Agenesis of the corpus callosum, infantile spasms, ocular anomalies (Aicardi's syndrome). Neurology 26:1152-1158, 1976.
